The invention relates to a novel process and novel intermediates for preparing substituted arylpyrazoles which are known as intermediates for herbicides.
A number of processes for preparing herbicidally active arylpyrazoles have already been disclosed; however, these processes afford the desired products in not quite satisfactory yields (cf. U.S. Pat. No. 5,281,571).
This invention, accordingly, provides a novel process for preparing substituted arylpyrazoles of the general formula (I) 
in which
R1 represents hydrogen or halogen,
R2 represents cyano or halogen,
R3 represents halogen, alkyl, halogenoalkyl or alkoxycarbonyl and
R4 represents option ally substituted alkyl,
characterized in that in a first step halogenoarenes of the general formula (II) 
in which
R1, R2 and R3 are each as defined above and
X represents halogen
are reacted with substituted alkines of the general formula (III) 
in which
Z represents 1-hydroxy-isopropyl or trimethylsilyl,
if appropriate in the presence of one or more reaction auxiliaries and if appropriate in the presence of a diluent, at temperatures between 50xc2x0 C. and 150xc2x0 C., the substituted arylalkines formed of the general formula (IV) 
in which
R1, R2, R3 and Z are each as defined above are reacted
if appropriate without intermediate isolation
in a second step with an alkali metal hydroxide or alkaline earth metal hydroxide and/or an alkali metal fluoride or alkaline earth metal fluoride, if appropriate in the presence of a reaction auxiliary and if appropriate in the presence of a diluent, at temperatures between 50xc2x0 C. and 150xc2x0 C., the arylalkines formed of the general formula (V) 
in which
R1, R2 and R3are each as defined above
are reacted in a third step with acylating agents of the general formula (VI)
R4xe2x80x94COxe2x80x94X1xe2x80x83xe2x80x83(VI) 
in which
R4 is as defined above and
X1 represents halogen or the group xe2x80x94Oxe2x80x94COxe2x80x94Oxe2x80x94R4,
if appropriate in the presence of one or more reaction auxiliaries and if appropriate in the presence of a diluent, at temperatures between 0xc2x0 C. and 150xc2x0 C. and the arylalkinones formed of the general formula (VII) 
in which
R1, R2 R3 and R4 are each as defined above
are reacted in a fourth step with hydrazine (hydrate), if appropriate in the presence of a diluent, at temperatures between 0xc2x0 C. and 150xc2x0 C.
Surprisingly, the substituted arylpyrazoles of the general formula (I) can be obtained in very high yields and in very good quality by the process according to the invention.
The process according to the invention thus represents a useful advance on the prior art.
The process according to the invention preferably relates to the preparation of compounds of the formula (I) in which
R1 represents hydrogen, fluorine or chlorine,
R2 represents cyano, fluorine or chlorine,
R3 represents halogen, C1-C6-alkyl, C1-C6-halogenoalkyl or C1-C6-alkoxy-carbonyl and
R4 represents optionally fluorine- and/or chlorine-substituted C1-C6-alkyl.
The process according to the invention in particular relates to the preparation of compounds of the formula (I) in which
R1 represents hydrogen, fluorine or chlorine,
R2 represents cyano or chlorine,
R3 represents fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxycarbonyl or ethoxycarbonyl and
R4 represents methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, each of which is optionally substituted by fluorine and/or chlorine.
Using, for example, in the first step 4-bromo-3-fluoro-2-methyl-benzonitrile and 2-methyl-3-butin-2-ol as starting materials, reacting in the next stage with sodium hydroxide and then further with dichloroacetyl chloride and finally with hydrazine hydrate, the course of the reaction in the process according to the invention can be outlined by the following formula scheme: 
The formula (II) provides a general definition of the halogenoarenes to be used as starting materials in the process according to the invention for preparing compounds of the formula (I). In the formula (II), R1, R2 and R3 each preferably or in particular have those meanings which have already been mentioned above, in connection with the description of the compounds of the formula (I) according to the invention, as being preferred or as being particularly preferred for R1, R2 and R3; X preferably represents chlorine, bromine or iodine, in particular bromine or iodine.
The starting materials of the formula (II) are known and/or can be prepared by known processes (cf. J. Am. Chem. Soc. 81 (1959), 5643; J. Org. Chem. 27 (1962), 1426-1430; loc. cit. 59 (994), 7238-7242; J. Med. Chem. 13 (1970), 713-722).
The compounds of the formula (II) are obtained, for example, when
(a) benzene derivatives of the general formula (VIII) 
in which
R1, R2 and R3 are each as defined above
are reacted with halogenating agents, such as, for example, chlorine, bromine or iodine, if appropriate in the presence of a catalyst, such as, for example, iron, at temperatures between 0xc2x0 C. and 50xc2x0 C. (cf. the Preparation Examples),
or when
(b) aniline derivatives of the general formula (IX) 
in which
R1, R2 and R3 are each as defined above
are reacted with sodium nitrite in the presence of a hydrohalic acid, such as, for example, hydrochloric acid (hydrogen chloride), hydrobromic acid (hydrogen bromide) or hydroiodic acid (hydrogen iodide), if appropriate in the presence of a catalyst, such as, for example, copper(l) chloride, copper(I) bromide or copper(I) iodide, at temperatures between 0xc2x0 C. and 50xc2x0 C.
The substituted alkines further to be used as starting materials in the process according to the invention for preparing compounds of the formula (I) are known chemicals for synthesis.
The first step of the process according to the invention is carried out in the presence of one or more reaction auxiliaries.
These include palladium (if appropriate in the presence of a support material, such as, for example, activated carbon), palladium complexes, such as, for example, palladium-bis-(triphenylphosphine) dichloride [bis-(triphenylphosphine)-palladium(II) dichloride] or tetrakis-(triphenylphosphine)-palladium, and also palladium salts, such as, for example, palladium(II) acetate or palladium(II) chloride, if appropriate in the presence of triphenylphosphine and if appropriate in the presence of copper compounds, such as, for example, copper(I) chloride, copper(I) bromide or copper(I) iodide, and alsoxe2x80x94if appropriate as further reaction auxiliariesxe2x80x94basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo[2,2,2]-octane (DABCO), 1,5-diazabicyclo[4,3,0]-non-5-ene (DBN), or 1 8 diazabicyclo[5,4,0]-undec-7-ene (DBU).
Suitable diluents for carrying out the process according to the invention are for all steps primarily inert organic solvents. These include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as acetone, butanone or methyl isobutyl ketone; nitriles, such as acetonitrile, propionitrile or butyrontrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; esters such as methyl acetate or ethyl acetate, and also sulphoxides, such as dimethyl sulphoxide.
When carrying out the first step of the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the first step is carried out at temperatures between 50xc2x0 C. and 150xc2x0 C., preferably between 80xc2x0 C. and 120xc2x0 C.
The first step of the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to carry out the first step of the process according to the invention under elevated or reduced pressure, in general between 0.1 bar and 10 bar.
For carrying out the first step of the process according to the invention, generally 0.1 to 100 mmol, preferably 1.0 to 50 mmol of a palladium complex, if appropriate 0.1 to 400 mmol, preferably 1.0 to 300 mmol, of triphenylphosphine, if appropriate 1.0 to 400 mmol, preferably 1 to 200 mmol, of a copper compound, and also, if appropriate, 1 to 100 mol, preferably 5 to 50 mol, of a basic organic nitrogen compound are employed per mole of halogenoarene of the formula (II).
In a preferred embodiment of the first step of the process according to the invention, the reaction components and reaction auxiliaries are mixed at room temperature and heated at the required reaction temperature until the reaction has ended. Work-up can be carried out in the customary manner. For example, the reaction mixture is filtered after the reaction has ended and the solvent is carefully distilled off from the filtrate under reduced pressure, the reaction product remaining as residue. However, it is also possible to employ the filtrate directly for the further reaction in the second step.
The second step of the process according to the invention is carried out using an alkali metal hydroxide or alkaline earth metal hydroxide and/or an alkali metal fluoride or alkaline earth metal fluoride. These include, for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, caesium hydroxide, magnesium hydroxide, calcium hydroxide and barium hydroxide and sodium fluoride, potassium fluoride, caesium fluoride and magnesium fluoride. Preference is given to using sodium hydroxide for carrying out the second step.
For the second step of the process according to the invention, a reaction auxiliary is preferably employed. Suitable reaction auxiliaries are in particular basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo[2,2,2]-octane (DABCO), 1,5-diazabicyclo[4,3,0]-non-5-ene (DBN), or 1,8 diazabicyclo[5,4,0]-undec-7-ene (DBU).
When carrying out the second step of the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the second step is carried out at temperatures between 0xc2x0 C. and 150xc2x0 C., preferably between 20xc2x0 C. and 120xc2x0 C.
The second step of the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to carry out the second step of the process according to the invention under elevated or reduced pressure, in general between 0.1 bar and 10 bar.
For carrying out the second step of the process according to the invention, generally 0.01 to 1.0 mol, preferably 0.1 to 0.5 mol, of alkali metal hydroxide or alkaline earth metal hydroxide and, if appropriate, 1 to 100 mol, preferably 5 to 50 mol, of reaction auxiliary are employed per mole of substituted arylalkine of the formula (IV).
In a preferred embodiment of the second step of the process according to the invention, the filtrate from the first step is admixed at room temperature with an alkali metal hydroxide or alkaline earth metal hydroxide, and the mixture is then heated at the required reaction temperature until the reaction is ended. Work-up can be carried out in a customary manner, for example by distillation under reduced pressure.
The formula (VI) provides a general definition of the acylating agents to be used as reaction components in the third step of the process according to the invention for preparing compounds of the formula (I). In the formula (VI), R4 preferably or in particular has those meanings which have already been mentioned above, in connection with the description of the compounds of the formula (I) according to the invention, as being preferred or as being particularly preferred for R4; X1 preferably represents fluorine, chlorine, bromine or the group Oxe2x80x94COxe2x80x94Oxe2x80x94R4, in particular chlorine.
The starting materials of the formula (IV) are known chemicals for synthesis.
The third step of the process according to the invention is carried out in the presence of one or more reaction auxiliaries.
These preferably include copper compounds, such as, for example, copper(I) chloride, copper(I) bromide or copper(I) iodide, andxe2x80x94preferably as further reaction auxiliariesxe2x80x94basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo-[2,2,2]-octane (DABCO), 1,5-diazabicyclo[4,3,0]-non-5-ene (DBN), or 1,8 diazabicyclo[5,4,0]-undec-7-ene (DBU).
When carrying out the third step of the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the third step is carried out at temperatures between 0C and 150xc2x0 C., preferably between 10xc2x0 C. and 120xc2x0 C.
The third step of the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to carry out the third step of the process according to the invention under elevated or reduced pressurexe2x80x94in general between 0.1 bar and 10 bar.
To carry out the third step of the process according to the invention, in general 0.9 to 2.0 mol, preferably 1.0 to 1.5 mol, of acylating agent of the formula (VI) and, if appropriate, 0.01 to 5.0 mol, preferably 0.1 to 2.5 mol, of reaction auxiliary are employed per mole of arylalkine of the formula (V).
In a preferred embodiment of the third step of the process according to the invention, arylalkine of the formula (V) and reaction auxiliary are mixed Keith the diluent andxe2x80x94preferably at slightly elevated temperaturexe2x80x94admixed with the acylating agent. The reaction mixture is thenxe2x80x94preferably at elevated temperature and, if appropriate, under elevated pressurexe2x80x94stirred until the reaction has ended. Work-up can be carried out after cooling in a customary manner, for example by washing with dilute hydrochloric acid and then with water, separating off the organic phase and careful distillative removal of the solvent from the organic phase under reduced pressure.
When carrying out the fourth step of the process according to the invention, the reaction temperatures can be varied over a relatively wide range. In general, the fourth step is carried out at temperatures between 0xc2x0 C. and 150xc2x0 C., preferably between 20xc2x0 C. and 120xc2x0 C.
The fourth step of the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to carry out the fourth step of the process according to the invention under elevated or reduced pressurexe2x80x94in general between 0.1 bar and 10 bar.
For carrying out the fourth step of the process according to the invention, generally 0.9 to 2.0 mol, preferably 1.0 to 1.5 mol, of hydrazine (hydrate) are employed per mole of arylalkinone of the formula (VII).
In a preferred embodiment of the fourth step of the process according to the invention, the reaction components are mixed at room temperature with a suitable solvent and the reaction mixture is heated until the reaction has endedxe2x80x94preferably on a water separator. Work-up can be carried out in the customary manner, for example by carefully distilling off the solvent under reduced pressure.
The substituted arylalkines of the general formula (IV) obtained in the first step of the process according to the invention, the arylalkines of the general formula (V) obtained in the second step and the arylalkinones of the general formula (VII) obtained in the third step have hitherto not been disclosed in the literature. The compounds of the general formulae (IV), (V) and (VII) therefore also form, as novel substances, part of the subject-matter of the present application.
The substituted arylpyrazoles of the formula (I) preparable by the process according to the invention can be employed as intermediates for preparing herbicidally active compounds (cf. U.S. Pat. No. 5281571).